Abstract

BackgroundMagnetosomes produced by magnetotactic bacteria represent magnetic nanoparticles with unprecedented characteristics. However, their use in many biotechnological applications has so far been hampered by their challenging bioproduction at larger scales.ResultsHere, we developed an oxystat batch fermentation regime for microoxic cultivation of Magnetospirillum gryphiswaldense in a 3 L bioreactor. An automated cascade regulation enabled highly reproducible growth over a wide range of precisely controlled oxygen concentrations (1–95% of air saturation). In addition, consumption of lactate as the carbon source and nitrate as alternative electron acceptor were monitored during cultivation. While nitrate became growth limiting during anaerobic growth, lactate was the growth limiting factor during microoxic cultivation. Analysis of microoxic magnetosome biomineralization by cellular iron content, magnetic response, transmission electron microscopy and small-angle X-ray scattering revealed magnetosomal magnetite crystals were highly uniform in size and shape.ConclusionThe fermentation regime established in this study facilitates stable oxygen control during culturing of Magnetospirillum gryphiswaldense. Further scale-up seems feasible by combining the stable oxygen control with feeding strategies employed in previous studies. Results of this study will facilitate the highly reproducible laboratory-scale bioproduction of magnetosomes for a diverse range of future applications in the fields of biotechnology and biomedicine.

Highlights

  • Magnetosomes produced by magnetotactic bacteria represent magnetic nanoparticles with unprecedented characteristics

  • In the widely studied alphaproteobacterium Magnetospirillum gryphiswaldense each step is highly regulated by a set of more than 30 genes leading to the formation of single crystalline magnetite particles with defined size, shape and magnetic properties, which are so far unmatched by magnetic nanoparticles produced by

  • Magnetosomes are of great potential in the biomedical and biotechnological field, and isolated magnetosomes were already successfully applied for cancer treatment, such as magnetic hyperthermia [8,9,10], phototherapy [11] and radiosensitization [12], as contrast agent for magnetic imaging [13,14,15,16] and as a tool in immune assays [17]

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Summary

Introduction

Magnetosomes produced by magnetotactic bacteria represent magnetic nanoparticles with unprecedented characteristics. Their use in many biotechnological applications has so far been hampered by their challenging bioproduction at larger scales. Magnetosomes are membrane-enveloped magnetite ­(Fe3O4) or greigite (­Fe3S4) crystals produced by magnetotactic bacteria for orientation along the Earth’s magnetic. In the widely studied alphaproteobacterium Magnetospirillum gryphiswaldense each step is highly regulated by a set of more than 30 genes leading to the formation of single crystalline magnetite particles with defined size, shape and magnetic properties, which are so far unmatched by magnetic nanoparticles produced by. The most robust and widely used strain for magnetosome engineering and bioproduction is M. gryphiswaldense, which produces up to 60 cuboctahedral magnetite crystals with 20–50 nm in diameter [28, 29]

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